No effect of 41-carotene supplementation on plasma 730 Am J C/in Nutr 1994:60:730-4. Printed in USA. © 1994 American Society for Clinical Nutrition lipoproteins in healthy smokers13 Geert van Poppel, Jeannette Hospers, Rien Buytenhek, and Hans MG Princen ABSTRACT A high intake of /3-carotene has been associ- ated with a decreased risk for cardiovascular disease. To evaluate whether fl-carotene intake may exert a protective effect through an impact on lipoprotein metabolism, we conducted a random- ized, double-blind trial in healthy, male cigarette smokers. Total cholesterol, high-density-lipoprotein (HDL) cholesterol, apoli- poprotein A-I (apo) A-I, apo B- 1 00, and lipoprotein(a) were mea- sured before and after 14 wk of treatment with /3-carotene (20 mg/d, n = 25) or placebo (n = 25). The fl-carotene and placebo groups were comparable with respect to all initial characteristics, but initial apo B-lOO was significantly higher in the 3-carotene group ( I .23 vs I .44 gIL). During the intervention, plasma con- centrations of 3-carotene increased 1 5-fold in the treatment group. Mean concentrations of total and HDL cholesterol, lipo- protein(a), apo A-I, and apo B-l00 did not change significantly in either group. We conclude that a 20 mg /3-carotene supple- mentid does not influence plasma lipoproteins in healthy male smokers. Am J C/in Nutr l994;60:730-4. KEY WORDS /3-Carotene, lipoproteins, high density lipo- protein, HDL, cholesterol, apolipoprotein A-I, apolipopnotcin B- 100, lipoprotein(a), cigarette smoking, humans, intervention Introduction Several epidemiological studies have reported an inverse re- lationship between /3-carotene intake and cardiovascular disease ( I -3). Rimm et al (4) found a lower relative risk (RR) for con- onary disease in smokers with a high intake of 3-carotene in the Health Professionals Follow-up Study (highest quintile of dietary intake compared with lowest: RR = 0.30). A recent multicenter case-control study indicated an inverse association between /3- carotene in fat biopsies and risk for myocardial infarction (5). Moreover, preliminary results from the Physicians’ Health Study suggest a reduction by 49% in cardiovascular morbidity and mor- tality in physicians with angina pectoris after supplementation of 50 mg /3-carotene on alternate days (6). Several mechanisms for a protective action of /3-carotene have been suggested. /3-carotene is an antioxidant (7, 8) and could thus prevent free radical-induced oxidative damage to low density lipoprotein (LDL), which may be a crucial event in the devel- opment of arteriosclerosis (9). However, we and others have demonstrated no effect of a I 4-wk /3-carotene supplementation on in vitro copper-induced LDL oxidation (10, 1 1). Another pos- sible mechanism of /3-carotene could be through conversion of /3-carotene to retinoids ( 1 2). Recently, it has been shown that retinoids are capable of stimulating apolipoprotein A-I (apo) A-I synthesis by induction of gene transcription in hepatocyte cultures ( I 3). Apo A-I is the major protein constituent of plasma high density lipoprotein (HDL) and this mechanism could thus explain the rise in HDL cholesterol reported by Ringer et al (14) in human volunteers after supplementation with /3-carotene. However, Nierenbeng et al ( 15) did not observe an effect of /3- carotene on HDL cholesterol in patients in a skin cancer preven- tion study. Possibly, effects of /3-carotene can only be observed in susceptible subjects who have low plasma concentrations of both HDL cholesterol and /3-carotene, as is the case in cigarette smokers(16-18). In the study by Ringcnetal(l4), smokers were not included, whereas Nierenbeng et al (15) do not give infor- mation on smoking habits. We therefore evaluated the effect of /3-carotene supplementation on lipoproteins in smokers who par- ticipated in a recently completed 14-wk trial on markers for can- cer risk (19, 20). In addition to HDL cholesterol and apo A-I, we also measured total cholesterol and the LDL protein constituent apo B- I 00 to monitor possible adverse effects. Finally, we in- vestigated the effect of /3-carotene on plasma concentrations of lipoprotein(a), a known independent risk factor for cardiovas- cular disease (21). Subjects and methods Studs’ design For this study, lipoproteins were assessed in a subgroup of subjects from an intervention trial on /3-carotene and biomarkers for cancer risk (19, 20). Healthy male employees of the AMEV Insurance Company, the Taxation Office, and the Power Corn- pany at Utrecht, Netherlands, participated in the intervention trial and gave their informed consent. The protocol was approved by an External Review Board for experiments with human volun- teens. All participants had smoked 15 cigarettes/d for > 2 y, did not use preparations containing netinol on carotenoids, and I From the Department of Epidemiology. Netherlands Organization for Applied Scientific Research (TNO) Nutrition and Food Research In- stitute, Zeist, and the Gaubius Laboratory, TNO Prevention and Health Research, Leiden, Netherlands. 2 Supported by the Dutch Prevention Foundation. S Address reprint requests to G van Poppel, Department of Epidcmi- ology. TNO Nutrition and Food Research Institute. P0 Box 360, 3700 Al Zeist. Netherlands. Received November 29, 1993. Accepted for publication June 10. 1994. by guest on August 7, 2014 ajcn.nutrition.org Downloaded from